Association of ABC gene profiles with time to progression and resistance in ovarian cancer revealed by bioinformatics analyses
CANCER MEDICINE
Authors: Seborova, Karolina; Vaclavikova, Radka; Soucek, Pavel; Elsnerova, Katerina; Bartakova, Alena; Cernaj, Petr; Bouda, Jiri; Rob, Lukas; Hruda, Martin; Dvorak, Pavel
Abstract
Introduction Ovarian cancer (OC) represents a serious disease with high mortality and lack of efficient predictive and prognostic biomarkers. ATP-binding cassette (ABC) proteins constitute a large family dedicated to active transmembrane transport including transport of xenobiotics. Materials and methods mRNA level was measured by quantitative RT-PCR in tumor tissues from OC patients. Bioinformatics analyses were applied to two gene expression datasets (60 primary tumors and 29 peritoneal metastases). Two different approaches of expression data normalization were applied in parallel, and their results were compared. Data from publically available cancer datasets were checked to further validate our conclusions. Results The results showed significant connections between ABC gene expression profiles and time to progression (TTP), chemotherapy resistance, and metastatic progression in OC. Two consensus ABC gene profiles with clinical meaning were documented. (a) Downregulation of ABCC4, ABCC10, ABCD3, ABCE1, ABCF1, ABCF2, and ABCF3 was connected with the best sensitivity to chemotherapy and TTP. (b) Oppositely, downregulation of ABCB11 and upregulation of ABCB1 and ABCG2 were connected with the worst sensitivity to chemotherapy and TTP. Results from publicly available online databases supported our conclusions. Conclusion This study stressed the connection between two well-documented ABC genes and clinicopathological features-ABCB1 and ABCG2. Moreover, we showed a comparable connection also for several other ABC genes-ABCB11, ABCC4, ABCC10, ABCD3, ABCE1, ABCF1, ABCF2, and ABCF3. Our results add new clinically relevant information to this oncology field and can stimulate further exploration.
ATP-binding cassette sub-family F member 1 (ABCF1) is identified as a putative therapeutic target of escitalopram in the inflammatory cytokine pathway
JOURNAL OF PSYCHOPHARMACOLOGY
Authors: Powell, Timothy R.; Tansey, Katherine E.; Breen, Gerome; Farmer, Anne E.; Craig, Ian W.; Uher, Rudolf; McGuffin, Peter; D'Souza, Ursula M.; Schalkwyk, Leonard C.
Abstract
The inflammatory cytokine pathway may be a potential therapeutic target for major depressive disorder (MDD). Previous reports suggest that antidepressants have anti-inflammatory properties and can cause a reduction in proinflammatory cytokines. Recent evidence suggests this might be mediated at the level of the transcriptome. The current study investigated the transcription of 86 genes in the inflammatory cytokine pathway both at baseline and after eight weeks of escitalopram treatment in MDD patients who were either clinical responders (n=25) or non-responders (n=21), using a subset of samples in the Genome-Based Therapeutic Drugs for Depression project (GENDEP). Changes in expression between baseline and eight weeks of treatment were assessed using two-tailed t-tests. To establish if any significant expression changes related to clinical response, the magnitude of the relative expression change between baseline and eight weeks of treatment was established and binary logistic regressions were used to compare differences between responders and non-responders. ATP-binding cassette sub-family F member 1 (ABCF1), a translational regulator of the inflammatory cytokine pathway showed a significant increase in expression after escitalopram treatment which was significantly greater in responders compared to non-responders, suggesting that ABCF1 may play a role in mediating antidepressant response.